The present invention relates to compositions and the use thereof of proteolytic enzymes developed for the hydrolysis of food-related proteins for treatment of conditions associated with hyperkeratotic mammalian tissue.
Hyperkeratotic tissue in mammals and the conditions arising therefrom result from abnormal processes within the skin. The top layer of skin, known as the stratum corneum, is composed primarily of cells that are dehydrated keratin protein. In a normal process called keratinization, epidermal cells are gradually pushed to the surface by underlying dermis cells where they exfoliate. In abnormal processes, i.e., when these cells do not exfoliate, they accumulate on the surface to form hyperkeratotic tissue causing discomfort. Hyperkeratotic tissue in mammals includes tylomas (calluses and fissures), helomas (corns), keratoses (papules), and dry skin scales and flakes. Common methods for managing hyperkeratinized tissue are the application of acids in lotion or cream carriers, moisturizing creams or lotions or mechanical scraping. Acids and scraping are disadvantageous because they tend to irritate normal epidermis and moisturizing creams are not effective in reducing hyperkeratotic tissue density.
Calluses and corns, usually found on the feet and hands, are thickened areas of normal skin which have formed to protect underlying bone from excessive weight bearing, pressure or friction. Foot callus appears most commonly on the sole and heel. Hand callus typically forms on the pads of the palm where pressure is most commonly exerted in handling tools and objects. When a callus deposits dead cells at its epicenter, it becomes a corn (heloma), a painful, conical hyperkeratosis. Corns are usually found over toe joints and between the toes and are typically caused by hammertoe, bone spurs or ill-fitting footwear impinging against skin. Calluses and corns cause walking discomfort and are commonly treated by rubbing off the hardened skin with a pumice stone or other scraping device, applying salicylic acid, or, if severe, by bone surgery to correct the underlying pressure point. Salicylic acid is effective for the removal of callus and corns but presents the risk of harming adjacent healthy tissue which is also exfoliated. Salicylic acid is also not recommended for use by the elderly with thinned skin, diabetics or by those with poor circulation or compromised immune systems, as the acid can result in open lesions which are then subject to infection.
Dry skin is a normal consequence of aging and is aggravated by cold, dry or windy climatic conditions. Treatment unusually involves the use of moisturizers after bathing, including petrolatum, lanolin, urea, alpha hydroxy acids, lactic acid or ammonium lactate to reduce scaling and help the skin hold water.
Eczema
Eczema is a general term encompassing various inflamed skin conditions that include dry, red, scaly, extremely itchy regions typically on the face, neck, inside of elbows, knees and ankles, and on feet and hands. About 15 million people suffer from eczema in the United States and about 15% of infants show symptoms but outgrown the condition with age. In some cases of eczema the skin can become leathery and thickened. A common form of eczema is atopic dermatitis, the symptoms of which are due, it is believed, to an abnormal response to the body""s immune system, or as a response to irritating substances coming in contact with the skin. There is no known cure and the condition is not contagious. Disease management is achieved by avoidance of triggers or medication.
Prevention of flares include a variety of measures designed to avoid irritating the skin or allowing it to become excessively dry, such as using moisturizers and anti-itch creams, avoiding sudden temperature changes, lowering stress, avoiding harsh chemicals, such as detergents, or scratchy materials such as wool, and restricting sensitizing food and environmental pollutants such as molds, pollens, or animal dander. Medications include corticosteroids, antihistamines, coal tar treatments, phototherapy and for more severe cases cyclosporine A and topical immunomodulators such as tacrolimus.
Cuticles
The skin covering the margins of the fingernail and toenail is called the cuticle. It can become hardened by frequent exposure to irritants such as soaps, detergents and chemicals, or by physical abuse, due to nail biting, gardening without hand protection, or exposure to extreme cold-weather. Current methods of managing hardened or enlarged nail cuticle include use a variety of manicure tools to cut away the thickened or raised areas. This can have the undesirable effect of generating a new layer of cuticle to replace that which is removed, or, in some cases, leaving exposed dermis at risk for infection or irritation. A healthy cuticle is soft and transparent with an even contour. A damaged cuticle is ragged, dry and thickened, opaque and adheres tightly to the nail plate, sometimes extending onto it. There are many cuticle creams available to improve damaged cuticles. These include skin softeners, skin moisturizers and acids.
Nail biting often extends to biting of the cuticle. This leads to tears and splitting of fingernail cuticles, which, once pulled away from the epidermis, dry to form a hard crust of skin especially around the lower arch of fingernails.
The present invention is directed to novel compositions and methods for treatment of hyperkeratotic mammalian tissue employing proteolytic enzymes originally developed for the hydrolysis of food-related proteins and currently commonly used as food grade meat tenderizers and flavor enhancers. Surprisingly, the inventor has discovered that these novel compositions containing these proteinases safely soften, thin and exfoliate hyperkeratotic formations on the skin, including calluses, corns, dry, scaling/flaking skin and keratoses. Specifically, when placed in a suitable carrier for dermatological use and applied regularly to the skin with or without occlusion, such proteinases and proteolytic enzymes selectively lyse hyperkeratotic tissue resulting in its softening, smoothing, thinning and exfoliation without harm to non-hyperkeratotic tissue. Such enzymes accomplish this by lysing only the 10-end peptide bonds of keratin protein, the dominant protein component of hyperkeratotic skin. These agents have minimal effect on normal skin because healthy epidermis lacks keratin, other than what exists in a fine layer of dead skin cells associated with normal sloughing. An example of an appropriate proteinase enzyme for the foregoing uses is Subtilisin Carlsberg manufactured as Alcalase(copyright) Food Grade by Novo Corporation. Another example is a fungal protease/peptidase complex produced by submerged fermentation of a selected strain of Aspergillus oryzae, sold by Novo Corporation as Flavourzyme(trademark) flavor enhancer.
Enzymes which digest proteins are widely distributed in nature. For example, U.S. Pat. No. 5,213,978 discloses extracellular proteases from Micrococcus sedentarius which are capable of solubilizing human callus material. However, the present invention employs proteolytic enzymes that selectively desquamify hyperkeratotic mammalian tissue. Tests conducted under bilateral, placebo-controlled, double blind conditions evidenced no irritation to adjacent normal skin and a 50% reduction in hardness and density within 14 days of nightly application to foot callus.
Selective desquamification of callus, corn and keratoses is possible because normal skin lacks the proteins containing 10-end peptide bonds which are broken by proteolytic enzymes. Products currently employed to treat callus, corns, keratoses and dry skin generally contain acids which can irritate normal skin and can cause burns of healthy tissue which can lead to infection.
Surprisingly, formulations according to the present invention are effective in controlling the symptoms of eczema. In a preferred embodiment at least one of the proteases of the present invention are provided in a petroleum base and the formulation is applied topically to the area of the skin exhibiting eczema. It is believed the protease(s) break down the affected tissue including any scales and thickened or leathery epidermis.
The invention is also useful for the removal, or exfoliation, of dead cells at the surface of the skin known as the stratum corneum, providing a smoother texture to the skin such as but not limited to the skin of the face, particularly when used as a night ointment for the prevention of wrinkles and lines and the reduction in the appearance of fine lines and wrinkles. In a preferred embodiment the invention comprises for example a petrolatum base, which serves as both a carrier of the enzyme/protease mixture and as a moisture barrier to retain facial moisture/prevent dryness. The ointment may be used nightly or once a week, depending on the age and condition of the epidermis.
The protease petrolatum ointment formula described in the application gently thins and softens dry, hyperkeratotic and hardened cuticles of the fingernails and toenails. The dead cells that build up in nail cuticle can be removed with once or twice daily application of the invention. Cuticles that are ragged or raised from the nail plate can be thinned, softened and over time exfoliated, resulting in a more attractive appearance and better protection of the nail plate margin. As a result, there is less resort to cutting with manicure tools or cuticle biting to remove loose skin, and the resulting cosmetic and infection problems than can ensue.
The present invention provides several unique advantages over the prior art.
The present invention provides novel compositions for treatment of hyperkeratotic mammalian tissue said compositions containing known proteolytic enzymes originally developed for the hydrolysis of food-related proteins wherein these novel compositions containing these proteinases safely soften, thin and exfoliate hyperkeratotic formations on the skin, including calluses, corns, dry, scaling/flaking skin and keratoses.
The present invention further provides methods for administering novel compositions containing proteolytic enzymes for treatment of hyperkeratotic mammalian tissue.
The present invention still further provides novel compositions for exfoliating hyperkeratotic mammalian tissue at body temperature and at neutral pH.
The present invention further provides a method for administering proteolytic enzymes in a suitable carrier for dermatological use and applied regularly to the skin with or without occlusion, wherein such proteolytic enzymes selectively lyse hyperkeratotic tissue resulting in its softening, smoothing, thinning and exfoliation without harm to non-hyperkeratotic tissue.